SUHW4

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Template:Short description Template:Infobox gene Zinc finger protein 280D, also known as Suppressor Of Hairy Wing Homolog 4, SUWH4, Zinc Finger Protein 634, ZNF634, or KIAA1584, is a protein that in humans is encoded by the ZNF280D gene located on chromosome 15q21.3.[1][2]

Gene

There are a total of 24 possible exons in any variant of the ZNF280D gene.[3] ZNF280D is oriented on the minus strand of Chromosome 15 and spans 288.396 kb.[4] Surrounding genes at the same locus include TEX9, HMGB1P33, MNS1, LOC645877, and LOC145783.[5]

File:ZNF280D Gene Location.PNG
Chromosomal location of the ZNF280D gene in humans with surrounding local genes
File:ZNF280D Chromosome Location.PNG
Chromosome 15 Location

mRNA

At least 24 spliced variants have been identified.[6] There are 7 probable alternative promoters. The mRNAs appear to differ by truncation of the 5' end, truncation of the 3' end, presence or absence of 12 cassette exons, overlapping exons with different boundaries, splicing versus retention of 5 introns.[6] The longest splice form contains 4428 bp.[7]

File:AceView Alternative Splicing.PNG
Most abundant alternative splice forms of ZNF280D mRNA.

Protein

Composition and Domains

File:DUF4195 MSA.PNG
Multiple sequence alignment of orthologs for DUF4195 reveals low conservation.
File:MSA zinc finger domains.PNG
Multiple sequence alignment of orthologs for five zinc finger domains reveals high conservation.

The ZNF280D protein is 979 amino acids in length.[8] The protein contains a domain of unknown function (DUF4195) spanning from amino acid 45 to amino acid 230.[8] DUF4195 (pfam13826) is a family that is found at the N-terminus of metazoan proteins that carry PHD-like zinc-finger domains; the function is unknown.[9] ZNF280D protein also contains five highly conserved Cys2His2-type zinc finger domains.[10] Zinc fingers have the ability to bind DNA, which supports the speculative role of ZNF280D as a transcription factor.[11] The protein has a weight of approximately 109.3 kdal.[12] Charge cluster analysis reveals a negative charge cluster near the N-terminus from amino acids 16-43.[12] Charge clusters are associated with functional domains of cellular transcription factors, providing further support for ZNF280D as a possible transcription factor.[13]

Interactions

ZNF280D has been experimentally determined to interact with CBX5 and CBX3 proteins.[14] These proteins both play a role in the formation of heterochromatin, which presents a possible functional role of ZNF280D as a transcriptional repressor.[15][16]

SNPs

There are a number of SNPs that have been observed in the human population.[17] The image below lists some of the most frequently occurring.

File:SNPs.PNG
Frequently observed SNPs in human genome.

Regulation

mRNA Level

File:Human ZNF280D Promoter and Predicted TF Binding Sites.pdf
Human ZNF280D promoter region and predicted transcription factor binding sites.

A number of transcription factors are predicted to bind to the predicted promoter region.[18]

Protein Level

ZNF280D protein contains 66 serine, 17 threonine, and 6 tyrosine residues all of which are potential phosphorylation sites.[19]

File:Phosphorylation human sites.PNG
Candidate phosphorylation sites in human ZNF280D protein.

The glycine residue at position 2 is a probable candidate for N-terminal acetylation.[20] There are seven probable sumoylation sites.[21]

File:Sumoylation Sites.PNG
Probable sumoylation sites in ZNF280D protein.

Expression

File:GEO Profile.PNG
GEO Profile expression analysis of ZNF280D protein in human tissues.

ZNF280D is ubiquitously expressed at relatively low levels throughout almost all tissues in the human body.[22]

In one study, the expression of ZNF280D was compared between endothelial progenitor cells in cord blood and peripheral blood. The results show that expression was significantly higher in cord blood. This supports a possible involvement of ZNF280D in embryonic development or cell differentiation.[23]

File:Endothelial progenitor study snip.PNG
Expression data for ZNF280D in endothelial progenitor cells from cord blood and adult peripheral blood.

Evolution

A number of orthologs and distant homologs have been identified for the human ZNF280D protein. There are also four paralogs to ZNF280D in the human genome.[24]

Protein Name Species Date of Divergence (Million Years Ago)[25] Accession Number Sequence Length (# amino acids) Sequence Identity E Value
ZNF280D Mouse (Mus musculus) 92.3 NP_666336 974 76% 0
ZNF280D Isoform X1 Cow (Bos taurus) 94.2 XP_002690904 974 88% 0
ZNF280D African bush elephant (Loxodonta africana) 98.7 XP_003418437 979 90% 0
ZNF280D Isoform X1 Chinese softshell turtle (Pelodiscus sinensis) 296 XP_006112544 993 61% 0
ZNF280D Saker falcon (Falco cherrug) 296 XP_005435548 939 60% 0
ZNF280D Ground tit (Pseudopdoces humilis) 296 XP_005521527 936 57% 0
ZNF280D Isoform X1 Chinese alligator (Alligator sinensis) 296 XP_006018037 277 50% 1E-64
ZNF280D Western clawed frog (Xenopus tropicalis) 371.2 XP_002940298 1071 49% 0
ZNF280D Isoform X1 Zebrafish (Danio rerio) 400.1 XP_005166581 879 43% 2E-172
ZNF280D-like Acorn worm (Saccoglossus kowalevskii) 661.2 XP_006811912 733 32% 5E-50
Zinc Finger Protein 36 Sea squirt (Ciona intestinalis) 722.5 NP_001041459 581 32% 7E-58
GL11474 Fruit fly (Drosophila persimilis) 782.7 XP_002016218 1271 29% 5E-16
Zinc Finger Protein Eye worm (Loa loa) 937.5 XP_003139663 495 33% 6E-19
Zap1p Yeast (Saccharomyces cerevisiae S288c) 12158 NP_012479 880 33% 2E-7
Table of select number of orthologs and distant homologs for human ZNF280D protein
Paralog Name Accession Number Sequence Length (# amino acids) Sequence Identity E Value
ZNF280C NP_060136 737 68% 0
ZNF280B NP_542942 543 54% 0
ZNF280A NP_542778 542 49% 6E-148
ZNF280E (pogo transposable element with ZNF domain isoform 1) NP_055915 1410 44% 4E-134
Table of paralogs for human ZNF280D protein

References

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Further reading

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